title: Pitx2c modulates cardiac-specific transcription factors networks in differentiating cardiomyocytes from murine embryonic stem cells.
abstract: OBJECTIVE
  The knowledge of the molecular signals that control cell differentiation into cardiomyocytes is critical to apply cell-based therapies and repair an injured heart. The transcription factor Pitx2 has essential roles in the development of different organs including the heart. Although a direct role of Pitx2 in the developing myocardium has recently been reported, the molecular pathways driven by Pitx2 as well as its cardiac target genes remain largely unexplored. The aim of this study was to unravel the molecular mechanisms driven by Pitx2 during the process of cardiomyocyte differentiation in vitro in mouse embryonic stem cell-derived cardiomyocytes.
  
  
  RESULTS
  Pitx2c was overexpressed in the R1-embryonic stem cell line. mRNA levels and protein distribution of several specific cardiac genes were analyzed by real-time PCR and immunohistochemistry experiments in R1-embryonic stem cell-derived beating areas at different stages of in vitro differentiation. Our results show that overexpression of Pitx2c in embryonic stem cell-derived cardiomyocytes is able to dynamically upregulate several cardiac-enriched transcription factors such as Isl1, Mef2c and Gata4. Additionally, Pitx2c induces the expression of chamber-specific cardiac genes such as Tbx5, Nppa and Cx40. These data were validated in an in vivo model of Pitx2 loss of function.
  
  
  CONCLUSIONS
  Taken together, these results demonstrate that Pitx2 plays a major role reinforcing the transcriptional program of cardiac differentiation.
authors.affiliation: Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Lozano-Velasco
authors.forename: Ana
authors.initials: A
authors.lastname: Chinchilla
authors.forename: Sergio
authors.initials: S
authors.lastname: Martínez-Fernández
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Torres
authors.forename: Francisco
authors.initials: F
authors.lastname: Navarro
authors.forename: Gary E
authors.initials: GE
authors.lastname: Lyons
authors.forename: Diego
authors.initials: D
authors.lastname: Franco
authors.forename: Amelia E
authors.initials: AE
authors.lastname: Aránega
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2